Growth Hormone Secreting Pituitary Macroadenoma Research Articles

Endocrinologic Outcome Following Endonasal Transphenoidal Excision of Growth Hormone Secreting Pituitary Adenomas

Background: Endonasal Transphenoidal Approach for excision of pituitary adenomas has been gaining popularity over the traditional microsurgical approach. The objective of this study is to assess the rate of hormonal recovery following endonasal transphenoidal excision of growth hormone secreting pituitary macroadenoma in out center. Methods: In this prospective observational study all cases subjected to endonasal transphenoidal excision of growth hormone secreting pituitary adenoma, during the study period from January 2019 to December 2020 at National Neurosurgical Referral Center, Bir Hospital, Kathmandu were included in this study. Preoperative and postoperative patient characteristics were recorded. Hormonal remission was defined as normal insulin-like growth factor-1 level at 3 months follow-up. Results: A total of 24 cases were included. The mean age of acromegaly cases was 39.42±10.41 years (24-56 years), with male to female ratio of 0.71:1. Majority (9) of cases had a Knosp grade 1.Thirteen cases had a Wilson-Hardy Extension Grade 0. Majority (11) of cases had a Wilson-Hardy Invasion Grade I. Three cases developed post-operative CSF leak, which recovered after lumbar drainage with no sequel. Five cases developed epistaxis which resolved with nasal packing. Sixty three percent (15 cases) had normal IGF-1 levels at 3 months follow up. Conclusion: Endoscopic endonasal transphenoidal approach to excision of growth hormone secreting pituitary adenomas is a safe and effective modality at achieving hormonal control in our setting.

Acromegalic Arthropathy and Ossification of the Yellow Ligament Treated with an Interlaminar Full-Endoscopic Approach: A Case Report

Introduction: Acromegalic arthropathy is a cause of morbidity and functional disability, affecting large peripheral joint, especially the spine. Affected patients can suffer from lumbar and sciatic pain, with or without radiculopathy. Due to the severe arthrosis, stenosis with ossification of the ligamentum flavum can often occur. Patient history: This study presents a 57-year-old patient with acromegalic arthropathy resulting from a growth hormone secreting pituitary macroadenoma. He was previously submitted to transsphenoidal surgery and present a history of L4-L5 decompression due to disc herniation and bilateral knee arthroplasty. The condition evolved to an acute left lumbar sciatic pain and the patient was refractory to clinical and physical therapy treatment. Surgical procedure: Decompression and discectomy were performed through an interlaminar endoscopic approach. Cutting and diamond burs and Keirrinson-type forceps were used for decompression. Diamond burs were used in the calcified yellow ligament and in the intervertebral disc to remove the protruding disc.Imaging exams: Preoperative exams showed calcified disc herniation and stenosis, with ossification of the posterior longitudinal ligament. Postoperative exams showed good decompression, removal of the calcified disc herniation and ossification of the posterior longitudinal ligament.Patient follow-up: Immediate resolution of sciatica pain and neurological deficit, with a negative nerve stretching test. At one-year follow-up, the patient had no return of radicular symptoms.Conclusion: Endoscopic surgery can be a reliable treatment option in approaching patients with severe stenosis of the spinal canal associated with calcified disc hernias and ossification of the ligamentum flavum, even when submitted to previous surgeries. This approach also presents benefits of a minimally invasive surgery.

ODP314 Gynecomastia as the Initial Presentation of Acromegaly.

Abstract Acromegaly is caused by persistent hypersecretion of growth hormone. In the US, its prevalence is less 20,000 per year. It is noted that co-secretion of growth hormone and prolactin from a single pituitary adenoma is common. Prolactin is co-secreted in about 25% of patients with acromegaly. We present a case of middle-age man who initially presented to our clinic for evaluation of bilateral gynecomastia with hypogonadism and found to have growth hormone secreting pituitary macroadenoma with co-secretion of prolactin. A 50 year-old Caucasian male veteran with past medical history of hypertension, hyperlipidemia, pre-diabetes, carpal tunnel syndrome, obstructive sleep apnea was referred to our clinic for evaluation and management of 5 months history of bilateral gynecomastia. He also reported chronic fatigue and erectile dysfunction. He denied headache, vision changes, change in shoes or ring size. He had gynecomastia with a larger left breast with some tenderness to palpation with no nipple discharge. He has short stature with large hands and feet. Some skin tags were also noted on physical examination. He was found to have elevated prolactin of 49.3 ng/ml (2.64-13.13ng/ml) with normal thyroid function test. His morning total testosterone was also low at 186 ng/dl (250-1100 ng/dl) with LH of 2.81 mIU/ml (1.24-8.26 mIU/ml), FSH of 5.98 mIU/ml (1.27-19.26 mIU/ml). Since his prolactin was elevated, MRI brain was done that showed 2.3 cm pituitary macroadenoma close to cavernous sinuses with no optic chiasm compression. Other pituitary function tests showed an elevated IGF-1 of 585 ng/ml (52-328 ng/ml). His morning cortisol and ACTH were normal. Oral glucose tolerance test revealed that growth hormone was not suppressed (GH > 2.4ng/ml post OGGT) confirming growth hormone excess/Acromegaly. He was given a trial of octreotide but did not tolerate the medication. He underwent transsphenoidal hypophysectomy and developed transient post-operative diabetes insipidus requiring Desmopressin. His prolactin, IGF-1 and testosterone level had returned to normal after surgery and gynecomastia completely resolved. Repeat MRI in 6 months after surgery showed postoperative changes and OGTT showed that GH suppressed appropriately (GH < 0.1 ng/ml post OGTT) and IGF-1 was149 ng/ml. Prolactin and testosterone had remained in the normal range. Acromegaly presents organomegaly with coarse physical features, enlarged hands and feet but some early symptoms are hyperhidrosis and extremity swelling with arthritis. We describe a case of acromegaly that initially presented with gynecomastia and secondary hypogonadism with hyperprolactinemia that lead to the diagnosis of acromegaly. The gynecomastia resolved completely with treatment. We hope that our case report is for the clinicians to be aware that acromegaly can present with metabolic syndrome, hypogonadism with gynecomastia and hyperprolactinemia and include screening tests to help diagnose and treat these patients at the early stages of the disease. Presentation: No date and time listed

The possibilities and impossibilities of treating acromegaly 50 years ago illustrated by the Diane Arbus photograph, A Jewish giant at home with his parents in the Bronx, N.Y. 1970.

SummaryThe iconic photograph ‘A Jewish giant at home with his parents in the Bronx, N.Y. 1970’ by the famous American photographer Diane Arbus (1923–1971) shows the 2.34 m (7 ft. 8¼ in.) acromegalic giant Eddie Carmel (1936–1972) and his parents in the living room of their New York home. The picture is a typical example of Arbus’ style. The relationship between the artist and the tall subject is described. A growth hormone-secreting pituitary macroadenoma was unsuccessfully treated with two cycles of pituitary radiotherapy achieving a 7000 rad cumulative dose and by incomplete pituitary surgery. Hypopituitarism was treated according to medical standards in the 1960s and 1970s. The giant patient died of increased intracranial pressure and at autopsy a residual acidophil pituitary macroadenoma was found, but also a perisellar meningioma which was most probably induced by the high dose of pituitary radiotherapy. The case report illustrates the possibilities and impossibilities of treating acromegaly 50 years ago and demonstrates the potential risks of high dose pituitary radiotherapy (in acromegaly).Learning pointsAcromegaly is a very old disease.Therapy for acromegaly has evolved over the decades.In art museums one can come across artistic impressions of endocrine disorders.People suffering from disfiguring endocrine disorders like acromegaly were pre-WW2 ‘exposed’ in theaters and circuses.High dose pituitary radiotherapy can be associated with secondary brain tumor formation.

Transcavernous Approach to the Anteromedial Triangle for Residual Functional Pituitary Adenoma.

Surgical treatment of functional pituitary adenomas is as rule performed by transsphenoidal approach. However, when then lesion invades the parasellar structures and the cavernous sinus, the transsphenoidal removal of these adenomas is usually incomplete. In this video, we present the technical nuances of a transcavernous approach to the anterio-medial triangle for the resection of a residual functional pituitary adenoma. The patient is a 40-year-old male who was diagnosed with growth hormone secreting pituitary macroadenoma. He underwent two transsphenoidal resections in 2013 and 2016 with a small residue in the left cavernous sinus. Subsequently, due to a failure of biochemical remission despite medical management, a transcranial transcavernous surgery was performed. Brain magnetic resonance imaging showed a mass in the roof of the left cavernous sinus, located at the level of the anteromedial triangle, adherent to the clinoidal segment of the internal carotid artery (ICA). The computed tomographic scan showed an osteolysis of the inferior surface of the anterior clinoidal process. After performing an extended pterional craniotomy and an extradural clinoidectomy, the cleavage plane is extended between the temporal dura and the inner layer of the lateral wall of the cavernous sinus. Intraoperative Doppler and stimulation are used to localize the clinoidal segment of the ICA and the third cranial nerve, delimiting the anteromedial triangle. The lesion is progressively dissected and removed. An optic neuropexy with the previously harvested fat is performed in case of a complementary radio surgical treatment. The patient had an uneventful postoperative course and showed a biochemical remission at the 3-month follow-up. The link to the video can be found at: https://youtu.be/oHfugVtU-Nc .

Old Wine in a New Bottle: Acromegaly Presenting as Diabetic Ketoacidosis

Acromegaly is a rare disease characterised by chronic excess of Growth Hormone (GH) levels. Insulin signalling is impaired, gluconeogenesis is excess and peripheral insulin resistance is increased in acromegaly causing hyperglycaemia and diabetes. Diabetic Ketoacidosis (DKA) is a rare but known complication of diabetes in acromegaly. Most cases of acromegaly come into light due to the classical soft tissue changes in the face and extremities. A high index of suspicion is required to diagnose this condition in early stage. Here, a case of 22-years-old male presented with DKA and on investigation was found to have acromegaly due to a GH secreting pituitary macroadenoma. This management and subsequent follow-up of the case along with review of literature is also done. Such a presentation of acromegaly was rare but rewarding.

Heat Intolerance and Hyperhidrosis as the only Presenting Manifestations of Acromegaly: A Case Report

Acromegaly is a state of Growth Hormone (GH) excess characterised by coarse facial features, acral enlargement, hyperhidrosis, headache, visual disturbances and visceromegaly. The most common cause of acromegaly is pituitary adenoma. The average delay between onset of symptoms and diagnosis is about six years in acromegaly owing to its subtle clinical features at the disease onset.Early diagnosis is important to reduce the morbidities and mortality associated with acromegaly. Familiarisation of physicians with the signs and symptoms of the disease is an effective strategy for the early diagnosis of acromegaly. Here, the authors report a case of 38year-old female patient. After proper clinical examination, history and series of relevant investigations, the serum GH level was estimated and was found to be elevated (40 ng/mL). GH secreting pituitary macroadenoma presenting with heat intolerance and hyperhidrosis without the classical manifestations of acromegaly.

SAT-467 Gigantism Caused by Growth Hormone-Secreting Pituitary Macroadenoma: A Case Report

Background Gigantism is a rare condition where excessive secretion of growth hormone (GH) occurs before fusion of the epiphyseal growth plates. Clinical Case A 23-year-old Sri Lankan male presented to the Endocrine clinic with extreme tall stature, and was diagnosed to have pituitary gigantism. He had been the tallest in his class since 5 years old. Pubertal development from 12 years of age was normal. There was no history of headache, visual disturbance, galactorrhea or any hypogonadal symptoms. Family history was non-contributory. On examination, there were clinical features of frontal bossing, prognathism, and prominence of supra-orbital ridge. He was 196cm in height (calculated midparental height of 171cm) and at Tanner stage 5. Initial medical treatment was started with cabergoline for 1 year, before decision for surgical treatment was sought in Singapore. Initial laboratory investigations revealed an elevated serum insulin-like growth factor-1 (IGF-1) value of 577ng/mL (RR: 116-358ng/mL), and failure of GH suppression during an oral glucose tolerance test, with GH nadir of 3.99 ng/mL (RR: <1 to 13.4ng/mL, no gender nor age-specific cut offs were provided). Prolactin was 132 mIU/L (RR 77-274mIU/L) and total testosterone was 11 nmol/L (RR 5-30nmol/L). Basal cortisol, thyroid function test, and calcium levels were normal. Pituitary magnetic resonance imaging showed a hypo-enhancing focus in the left lateral aspect of the pituitary gland with extension into the sphenoid sinus, measuring 12mm in size at largest diameter, which was suspicious for a pituitary adenoma. He subsequently underwent transphenoidal surgery, and there were no immediate complications post operatively. During a follow up visit 3 months after surgery, laboratory investigations showed normalization of GH (0.33 ng/mL), IGF-1 (212 ng/mL) levels, and normal GH suppression during OGTT. Conclusion Pituitary gigantism occurs during the pre-pubertal period of active linear growth, where elevated GH and IGF-1 levels result in extreme growth acceleration and tall stature (1). The treatment of choice for well-circumscribed pituitary adenomas is transphenoidal surgery, which may be curative (2).

Long-Term Effects of Intracapsular Debulking and Adjuvant Somatostatin Analogs for Growth Hormone-Secreting Pituitary Macroadenoma: 10 Years of Experience in a Single Institute

Long-term effects of endoscopic endonasal transsphenoidal intracapsular debulking and adjuvant somatostatin analogs (SSAs) were evaluated in patients with growth hormone- (GH) secreting pituitary macroadenomas. We retrospectively reviewed the medical records of 45 patients with acromegalic macroadenoma who underwent endonasal endoscopic transsphenoidal intracapsular debulking and received adjuvant SSAs (octreotide) between 2006 and 2015 who had >1 year of follow-up. To evaluate the predictive factors for 1 year and long-term biochemical outcomes, univariate and multivariate analyses were performed. Biochemical remission was achieved in 1 year in 20 of the 45 (44.4%) patients, and in 31 of the 45 patients after long-term adjuvant SSA treatment. Tumor control was achieved in 43 of the 45 (93.3%) patients. The univariate analysis showed age (≥55 years), tumor size (diameter ≤1.5 cm), premedication GH levels (≤2.8 ng/mL), premedication insulin-like growth factor 1 levels (≤2-fold of upper limit of normal range), cavernous sinus invasion (Knops grades 2, 3, and 4), and near-total tumor resection were associated with long-term outcomes. The multivariate analysis showed near-total resection was a significant predictor for long-term outcomes (P= 0.019). There were no new pituitary dysfunctions. The observed complications included one case of cerebrospinal fluid leakage and one case of epistaxis requiring intervention. Intracapsular debulking and adjuvant SSAs are a safe and viable treatment for patients with GH secreting pituitary macroadenoma to achieve biochemical remission and tumor control. Although adjuvant SSA treatment enhances residual tumor control, cavernous sinus invasion impedes the remission of endocrine tumors.

THE MULTIMODAL MANAGEMENT OF GROWTH HORMONE-SECRETING PITUITARY MACROADENOMA

The expansive processes of the sellar region include tumors of mesenchymal, neural or epithelial origin, along with cystic and inflammatory processes. From the epithelial sellar tumors, almost 90 % are represented by pituitary adenomata – benign tumors which develop from the adenohypophyseal cells, accounting for approximately 10–15% of all intracranial expansive processes. According to the clinical criteria, the pituitary adenomata can be classified as endocrine-inactive or non-producing adenomata, and endocrine-active or producing adenomata. The non-producing adenomata represent approximately 39–50% of all pituitary tumors; the prolactinomata represent approximately 6.1%; the growth hormone producing adenomata approximately 27.9%; the adenocorticotropic hormone producing adenomata 6%; the thyrotropic producing hormone adenomata 0.4%; and the follicle-stimulating or luteinizing producing hormone adenomata are extremely rare. The surgical approach used on a large scale today in pituitary and suprasellar tumors is the transnasal transsphenoidal approach, which is less invasive compared to the standard transcranial approach and has got excellent results so far. The purpose of this article is to illustrate the main data about pituitary tumors, based on a case report presentation. At the same time, we aim to keep track of the latest information in the specialty literature, and focus on the neurosurgical aspects. The therapeutic strategy in the case of a 24-year-old female patient diagnosed with a growth hormone-secreting pituitary macroadenoma, with a suprasellar extension and an infrasellar one in the sphenoidal sinus and with invasion in the right cavernous sinus.

Growth hormone-secreting pituitary macroadenoma presenting concurrently with non-Hodgkin’s lymphoma and responding to doxorubicin treatment: case report and review of the literature

We present a case report of a patient who presented with nausea and vomiting, as well as acromegalic features. Following testing, a pituitary adenoma and mediastinal non-Hodgkin's lymphoma were diagnosed. Following two cycles of R-CHOP chemotherapy, imaging showed significant decrease in size of the sellar tumor. Following resection of tumor, both frozen and permanent section revealed only necrotic material. Further research into the potential utility of doxorubicin for the treatment of recurrent or refractory pituitary adenomas may be warranted.

A rare vascular complication of transsphenoidal surgery

We report a rare case of anterior cerebral artery (ACA) thrombosis following transsphenoidal surgery in a case of growth hormone secreting pituitary macroadenoma. During the surgery, there was arachnoid breach with cerebrospinal fluid (CSF) leak. Post operatively, she became blind in both eyes for which re-exploration was done. A computed tomographic (CT) scan 16hours after surgery showed a large tumor bed haematoma which was explored transcranially. During surgery, the right A1 was thrombosed while the ICA and middle cerebral artery (MCA) were patent as confirmed by post-operative magnetic resonance imaging (MRI). However, she died on the second post-operative day. ACA thrombosis following transsphenoidal surgery has not been reported before. A review of literature and possible mechanism of this complication has been discussed.

Expanded endonasal endoscopic approach for resection of a growth hormone-secreting pituitary macroadenoma coexistent with a cavernous carotid artery aneurysm

The co-existence of pituitary adenomas (PA) and carotid artery aneurysms has been described and may be particularly frequent in acromegaly. The co-occurrence of an intracranial aneurysm in the setting of a PA presents significant risk to the patient, particularly when the aneurysm is within or near the operative field. We describe a 48-year-old, right-handed female patient with a large skull base lesion who had a left cavernous carotid artery aneurysm detected on her preoperative imaging studies. This patient was managed using a staged approach. She first underwent endovascular stent-assisted coiling of the aneurysm followed, six months later, by resection of the tumor via an expanded endonasal endoscopic approach. Histopathological analysis revealed a pituitary macroadenoma with neuronal metaplasia. Angiographic embolization followed by an expanded endonasal endoscopic approach is a safe and effective treatment for such lesions. Vascular imaging studies and a low index for suspicion are required for preoperative identification of such complex situations.

Disappearance of a GH Secreting Macroadenoma, during Long-term Somatostatin Analogue Administration

Acromegaly is caused by excessive growth hormone secretion, usually from a pituitary adenoma. Increased mortality rate is reverted to that of the normal population after decreasing GH and IGF-I levels to less than 2-2.5 microg/liter and normal sex- and age-matched controls, respectively, regardless of the treatment employed. The use of somatostatin analogues as primary or adjunctive therapy has been widely applied in the management of acromegaly. A few cases have been reported in the literature, complete shrinkage of a pituitary GH secreting macroadenoma after long-term somatostatin analogue administration. We report a patient in whom long term (60 months) octreotide-L.A.R administration resulted in complete disappearance of a growth hormone secreting pituitary macroadenoma.

Successful Treatment of an Invasive Growth Hormone-Secreting Pituitary Macroadenoma in an 8 Year-old Boy

We describe an 8 year-old boy with growth acceleration due to an invasive growth hormone (GH)-secreting pituitary macroadenoma who was successfully treated with the somatostatin analogue octreotide prior to transsphenoidal microsurgery. His tumor was resected completely and the patient remains in remission.

Transient MR changes and symptomatic epilepsy following gamma knife treatment of a residual GH-secreting pituitary adenoma in the cavernous sinus

To report a rare side effect of gamma knife treatment of pituitary macroadenoma. In a forty-one-year old female patient acromegaly was diagnosed due to a growth hormone secreting pituitary macroadenoma. Following transsphenoidal surgery the patient underwent gamma knife treatment for persistent uncontrolled acromegaly activity of residual tumor, infiltrating the left cavernous sinus. 15 months later, complex partial seizures were diagnosed and 17 months after gamma knife treatment a gadolinium enhancing lesion was detected in her left medial temporal lobe. Radiation induced changes, radiation necrosis or a glioma were considered. Neuropsychological testing indicated potentially significant post-surgical deficits. Therefore, surgical action was postponed and anti-epileptic treatment was started. Four months later she was free of seizures and an MR scan showed an almost complete regression of the gadolinium enhancing lesion, indicating that it had been due to radiation induced changes. Gamma knife surgery of a pituitary adenoma may cause radiation induced MR changes of the mesial temporal lobe mimicking glioma or radionecrosis and cause symptomatic epileptic seizures. The awareness of this rare complication is important to avoid unnecessary and potentially harmful diagnostic or therapeutic interventions.

Disappearance of a growth hormone secreting macro adenoma during long-term somatostatin analogue administration and recurrence following somatostatin withdrawal

Acromegaly is caused by excessive growth hormone secretion, usually from a pituitary adenoma. The use of somatostatin analogues as primary or adjunctive therapy has been widely applied in the management of acromegaly. We are aware of only three reported cases of complete shrinkage of a pituitary adenoma after long-term analogue administration. However in these cases, the reduction in the dimension of the adenoma was obtained with the everyday use of somatostatin analogues and not with the newer longer acting formulations. We report a patient in whom long term (62 months) lanreotide-L.A.R administration resulted in complete disappearance of a growth hormone secreting pituitary macroadenoma, followed by recurrence of the adenoma six months post therapy discontinuation.

Growth Hormone-Secreting Pituitary Macroadenoma and Meningioma in a Woman—A Case Report and Review of the Literature

Co-existence of pituitary adenomas and meningiomas is rare. Extensive review of the literature reveals only 32 cases with this association if meningiomas appearing after radiation therapy for pituitary tumors are excluded. There is a female preponderance and the meningiomas are usually located in the immediate vicinity of the pituitary. Although it is likely caused by chance occurrence, genetic dysregulation leading to the development of these tumors can not be ruled out.

Reversible Shrinkage of a Growth Hormone-Secreting Pituitary Adenoma by a Long-Acting Somatostatin Analogue, Octreotide

Octreotide acetate (SMS-201-995), a somatostatin analogue, was used to treat an acromegalic patient harboring a growth hormone-secreting pituitary macroadenoma. Intermittent subcutaneous administration of octreotide suppressed growth hormone and insulin-like growth factor-I (IGF-I) levels and ameliorated clinical symptoms. Magnetic resonance imaging performed after 16 weeks revealed a 70% shrinkage of the pituitary mass, with a resultant partially empty sella turcica. To document that this shrinkage occurred as a result of octreotide treatment and not spontaneous tumor infarction, the medication was withdrawn for 4 weeks. A second magnetic resonance image disclosed regrowth of the tumor accompanied by rebound of growth hormone and IGF-I secretion. Subsequent biochemical remission has been sustained with preservation of anterior pituitary function since the drug was reinitiated. These findings suggest that intermittent subcutaneous administration of octreotide may provide potent medical ablation of growth hormone-secreting macroadenomas.